EU/3/15/1524

On 28 July 2015, orphan designation (EU/3/15/1524) was granted by the European Commission to Ultragenyx UK Limited, United Kingdom, for triheptanoin for the treatment of long-chain 3-hydroxyacyl-coA dehydrogenase deficiency.

What is long-chain 3-hydroxyacyl-coA dehydrogenase deficiency?

Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency is an inherited disease caused by the lack of an enzyme called LCHAD. LCHAD is one of the enzymes needed by the mitochondria (the energy-producing components within cells) to break down certain fatty acids in order to generate energy. If this enzyme is lacking, cells cannot function normally causing a wide range of signs and symptoms including hypoglycaemia (low blood sugar levels), abnormalities in the retina (the light-sensitive tissue at the back of the eye) and damage to the liver, brain, nerves and heart.

The condition is chronically debilitating and life-threatening, particularly since it causes hypoglycaemia and damage to the nerves and various organs.

What is the estimated number of patients affected by the condition?

At the time of designation, LCHAD deficiency affected approximately 0.8 in 10,000 people in the European Union (EU). This was equivalent to a total of around 41,000 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This isbased on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

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*Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed on the basis of data from the European Union (EU 28), Norway, Iceland and Liechtenstein. This represents a population of 512,900,000 (Eurostat 2015).

What treatments are available?

At the time of designation, no satisfactory methods were authorised in the EU for the treatment of LCHAD deficiency. Treatment of patients primarily involved restriction of dietary fat, as well as increased frequency of food intake to avoid overloading the body with fatty acids. However, these dietary regimens were of unproven value or only partially successful.

How is this medicine expected to work?

Triheptanoin is a synthetic (artificially produced) fat, which is broken down in the liver into substances that can be used to generate energy without the need for LCHAD. By bypassing the need for LCHAD, this medicine is expected to restore normal energy generation and ultimately improve the overall outcome of the patients.

What is the stage of development of this medicine?

The effects of the medicine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with triheptanoin in patients with long-chain 3-hydroxyacyl-coA dehydrogenase deficiency were ongoing.

At the time of submission, triheptanoin was not authorised anywhere in the EU for long-chain 3-hydroxyacyl-coA dehydrogenase deficiency. Orphan designation of the medicine had been granted in the United States for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 18 June 2014 recommending the granting of this designation.

Opinions on orphan medicinal product designations are based on the following three criteria:

• the seriousness of the condition;
• the existence of alternative methods of diagnosis, prevention or treatment;
• either the rarity of the condition (affecting not more than 5 in 10,000 people in the EU) or insufficient returns on investment.

Designated orphan medicinal products are products that are still under investigation and are considered for orphan designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.

The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.